Timing of Stent Thrombosis Influences Its Relationship With Mortality

Early stent thrombosis carries a higher risk of cardiac death compared with late or very late events in a broad range of CAD patients, according to a study published online March 24, 2015, ahead of print in the American Journal of Cardiology.

“While [stent thrombosis] remains infrequent, continued efforts to determine how to reduce [the complication], particularly within the first 30 days, are warranted,” Laura Mauri, MD, MSc, of Brigham and Women’s Hospital (Boston, MA), and colleagues write.

The researchers looked at pooled data from the PROTECT randomized trial—which assigned 8,709 patients undergoing PCI for indications ranging from stable angina to ACS to receive the Endeavor zotarolimus-eluting stent (Medtronic) or the Cypher sirolimus-eluting stent (Cordis/Johnson & Johnson)—and the PROTECT Continued Access trial—which included 1,018 patients treated with Endeavor.

Through a median follow-up of 4.1 years, the rate of Academic Research Consortium (ARC)-defined definite or probable stent thrombosis was 1.9%. That included 61 early events occurring within 30 days (0.6%), 27 late events occurring beyond 30 but within 360 days (0.3%), and 96 very late events occurring after 360 days (1.0%).

Patient characteristics generally did not differ across the 3 stent thrombosis groups, although diabetes was more common in patients who had late events. Endeavor was used in most patients who had early and late events, whereas Cypher was used in the majority of patients who had very late stent thrombosis. Late events were associated with a lower likelihood of achieving TIMI 3 flow after the procedure. Device success was less common in patients who experienced early stent thrombosis.

The percentage of patients using dual antiplatelet therapy (DAPT), which was recommended for 3 to 12 months or longer and consisted mostly of aspirin and clopidogrel, was 97.3% at discharge and 84.0% at 1 year, with no differences based on the timing of stent thrombosis.

At 4 years, patients with stent thrombosis at any point were more likely than those who did not develop the complication to die from cardiac causes (primary outcome; 32.1% vs 2.5%) and to have an MI (93.5% vs 14.3%; P < .001 for both).

The combined rate of cardiac death or MI did not vary by stent thrombosis timing, but differences emerged for the individual outcomes. MI incidence was higher for patients who had late and very late events compared with early events. In contrast, the rate of cardiac death was higher in patients with early stent thrombosis than in those with late or very late events (table 1).

Cardiac death occurring on the same day as stent thrombosis was more common in patients who had early events, and same-day MI was more frequently associated with late or very late events.

Stent type did not influence the relationship between the timing of stent thrombosis and outcomes. 

Findings Consistent With Some—but Not All—Prior Studies

The results are concordant with previous research that used prospective follow-up, including an analysis of the ARRIVE 1 and 2 registries.

“However, procedure-based registries lacking systematic, long-term follow-up have reported variable absolute rates of events,” Dr. Mauri and colleagues note. “Some challenges with the accurate ascertainment of clinical event rates in prior studies have included: nonstandardized criteria for outcomes; the exclusion of out-of-hospital events; and the lack of endpoint adjudication by an independent events committee.”

As an explanation for the higher risk of cardiac death associated with early stent thrombosis, the researchers point to differences in pathophysiological properties based on the timing of the events, “with early [stent thrombosis] typically related to procedural and technical factors and late and very late [events] more often associated with patient and lesion characteristics and DAPT duration.”

DAPT status at the time of stent thrombosis was not available, which represents a critical limitation of the study, according to Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center (New York, NY). This information, he said, would have provided more insight into the observed relationships with cardiac death.

Dr. Moses told TCTMD in a telephone interview that mechanistic differences between early and late events likely explained the higher rate of cardiac death with early events. Early stent thrombosis is more likely to be a purely thrombotic event related to stent deployment and dissections, but late and very late events are more likely to result from restenosis or neoatherosclerosis. Events occurring later also may allow for the development of more protective collateralization, he said.

Areas to concentrate on for the reduction of early events include stenting technique, stent design, and pharmacology, Dr. Moses suggested, noting that although late thrombosis is becoming less frequent and less consequential with newer-generation stents, early events are not decreasing.

“This paper helps us refocus on the early events, which still have profound consequences and haven’t gone away,” he said.

Source:
Secemsky EA, Matteau A, Yeh RW, et al. Comparison of short- and long-term cardiac mortality in early versus late stent thrombosis (from pooled PROTECT trials). Am J Cardiol. 2015;Epub ahead of print.

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